PROJECT SUMMARY There are very few controlled studies on the oral health of older HIV-infected individuals, especially postmenopausal women. This is of particular concern in the U.S, where more than half of HIV-infected individuals are over age 50. Our group has previously demonstrated that skeletal bone loss at the spine and hip is greater and fracture rates higher in HIV-infected than uninfected women after menopause. Our preliminary data also show that HIV-infected women over age 50 had greater alveolar bone loss and a trend for fewer teeth compared to age-matched uninfected controls. However, the separate and/or combined contribution of HIV infection and estrogen deficiency to oral immune activation and the observed alveolar bone loss is uncertain. Therefore, the goal of this study is to determine the extent and progression of periodontal disease in HIV-infected pre- and postmenopausal women on cART and to investigate the contribution of periodontal immune activation to its pathogenesis. We hypothesize that HIV-infection is associated with increased oral immune activation. Loss of the beneficial immune-modulatory effects of estrogen results in an increased inflammatory response to periodontal pathogens, and greater alveolar bone loss after menopause. In order to examine this, we propose three Specific Aims. Aim 1: To determine the impact of HIV infection and menopause on periodontal health in a cross sectional study 240 HIV-infected and uninfected pre- and post- menopausal women. HIV-infected postmenopausal women will have evidence of worsened clinical periodontal parameters, higher GCF inflammatory biomarkers, greater alveolar bone loss and fewer teeth than uninfected post-menopausal women, and both HIV-infected and uninfected pre-menopausal women. Aim 2: To define the oral immune response in HIV-infected and uninfected postmenopausal women during the induction and resolution of gingival inflammation using the experimental gingivitis model. The clinical, GCF and gingival tissue cytokine response during induction of gingivitis will be greater, and the resolution of the inflammatory response more attenuated in HIV-infected post-menopausal women compared to uninfected postmenopausal women or HIV-infected women on hormone replacement therapy. Aim 3: To delineate the clinical, oral immune, and alveolar bone response to standard-of-care periodontal treatment in HIV-infected and uninfected postmenopausal women with moderate periodontitis. Improvements in clinical periodontal parameters, GCF biomarkers, and alveolar bone density and microarchitecture will be less in HIV-infected than uninfected postmenopausal women with moderate periodontitis in response to oral hygiene instruction, scaling/root planing and periodontal maintenance. If proven correct, these studies provide rationale for investigating use of a selective estrogen receptor modulator (SERM), as a safe and testable intervention to prevent periodontal disease progression and/or alveolar bone loss in HIV-infected postmenopausal women.